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. 1982 Sep;77(1):153–161. doi: 10.1111/j.1476-5381.1982.tb09281.x

Protease inhibitor homologues from mamba venoms: facilitation of acetylcholine release and interactions with prejunctional blocking toxins.

A L Harvey, E Karlsson
PMCID: PMC2044661  PMID: 6751453

Abstract

1 Five polypeptides, which were isolated from elapid snake venoms and which are structurally related to protease inhibitors, were tested for action on isolated biventer cervicis nerve-muscle preparations of the chick. 2 Dendrotoxin from the Eastern green mamba (Dendroaspis angusticeps) and toxins K and I from the black mamba (Dendroaspis polylepis polylepis) increased to indirect stimulation without affecting responses to exogenous acetylcholine, carbachol of KCl. 3 The two other protease inhibitor homologues, HHV-II from Ringhals cobra (Hemachatus haemachatus) and NNV-II from Cape cobra (Naja nivea) did not increase responses to nerve stimulation. Trypsin inhibitor from bovine pancreas also had no facilitatory effects on neuromuscular transmission. 4 The facilitatory toxins from mamba venoms interacted with the prejunctional blocking toxins, beta-bungarotoxin, crotoxin and notexin, but not with taipoxin. The blocking effects of beta-bungarotoxin were reduced by pretreatment with the mamba toxins, whereas the blocking actions of crotoxin and notexin were enhanced. 5 The results indicate that protease inhibitor homologues from mamba venoms form a new class of neurotoxin, which acts to increase the release of acetylcholine in response to motor nerve stimulation. 6 From the interaction studies it is concluded that the facilitatory toxins bind to motor nerve terminals at sites related to those occupied by the prejunctional blocking toxins. However, differences in interactions with individual toxins suggest that there must be several related binding sites on the nerve terminals.

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Selected References

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  1. Barrett J. C., Harvey A. L. Effects of the venom of the green mamba, Dendroaspis angusticeps on skeletal muscle and neuromuscular transmission. Br J Pharmacol. 1979 Oct;67(2):199–205. doi: 10.1111/j.1476-5381.1979.tb08667.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bon C., Changeux J. P., Jeng T. W., Fraenkel-Conrat H. Postsynaptic effects of crotoxin and of its isolated subunits. Eur J Biochem. 1979 Sep;99(3):471–481. doi: 10.1111/j.1432-1033.1979.tb13278.x. [DOI] [PubMed] [Google Scholar]
  3. Caratsch C. G., Maranda B., Miledi R., Strong P. N. A further study of the phospholipase-independent action of beta-bungarotoxin at frog end-plates. J Physiol. 1981;319:179–191. doi: 10.1113/jphysiol.1981.sp013900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chang C. C., Su M. J. Effect of 3,4-diaminopyridine and tetraethylammonium on the presynaptic blockade caused by beta-bungarotoxin. Toxicon. 1980;18(4):481–484. doi: 10.1016/0041-0101(80)90057-4. [DOI] [PubMed] [Google Scholar]
  5. Chang C. C., Su M. J., Lee J. D., Eaker D. Effects of Sr2+ and Mg2+ on the phospholipase A and the presynaptic neuromuscular blocking actions of beta-bungarotoxin, crotoxin and taipoxin. Naunyn Schmiedebergs Arch Pharmacol. 1977 Sep;299(2):155–161. doi: 10.1007/BF00498557. [DOI] [PubMed] [Google Scholar]
  6. Chang C. C., Su M. J. Mutual potentiation, at nerve terminals, between toxins from snake venoms which contain phospholipase A activity: beta-bungarotoxin, crotoxin, taipoxin. Toxicon. 1980;18(5-6):641–648. doi: 10.1016/0041-0101(80)90092-6. [DOI] [PubMed] [Google Scholar]
  7. Durant N. N., Marshall I. G. The effects of 3,4-diaminopyridine on acetylcholine release at the frog neuromuscular junction. Eur J Pharmacol. 1980 Oct 17;67(2-3):201–208. doi: 10.1016/0014-2999(80)90499-9. [DOI] [PubMed] [Google Scholar]
  8. Fohlman J., Eaker D., Karlsoon E., Thesleff S. Taipoxin, an extremely potent presynaptic neurotoxin from the venom of the australian snake taipan (Oxyuranus s. scutellatus). Isolation, characterization, quaternary structure and pharmacological properties. Eur J Biochem. 1976 Sep 15;68(2):457–469. doi: 10.1111/j.1432-1033.1976.tb10833.x. [DOI] [PubMed] [Google Scholar]
  9. GINSBORG B. L., WARRINER J. The isolated chick biventer cervicis nerve-muscle preparation. Br J Pharmacol Chemother. 1960 Sep;15:410–411. doi: 10.1111/j.1476-5381.1960.tb01264.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Harris J. B., MacDonell C. A. Phospholipase A2 activity of notexin and its role in muscle damage. Toxicon. 1981;19(3):419–430. doi: 10.1016/0041-0101(81)90046-5. [DOI] [PubMed] [Google Scholar]
  11. Harvey A. L., Gage P. W. Increase of evoked release of acetylcholine at the neuromuscular junction by a fraction from the venom of the eastern green mamba snake (Dendroaspis angusticeps). Toxicon. 1981;19(3):373–381. doi: 10.1016/0041-0101(81)90042-8. [DOI] [PubMed] [Google Scholar]
  12. Harvey A. L., Karlsson E. Dendrotoxin from the venom of the green mamba, Dendroaspis angusticeps. A neurotoxin that enhances acetylcholine release at neuromuscular junction. Naunyn Schmiedebergs Arch Pharmacol. 1980 May;312(1):1–6. doi: 10.1007/BF00502565. [DOI] [PubMed] [Google Scholar]
  13. Harvey A. L., Marshall I. G. The actions of three diaminopyridines on the chick biventer cervicis muscle. Eur J Pharmacol. 1977 Aug 15;44(4):303–309. doi: 10.1016/0014-2999(77)90303-x. [DOI] [PubMed] [Google Scholar]
  14. Hendon R. A., Fraenkel-Conrat H. Biological roles of the two components of crotoxin. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1560–1563. doi: 10.1073/pnas.68.7.1560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ho C. L., Lee C. Y. Presynaptic actions of Mojave toxin isolated from Mojave rattlesnake (crotalus scutulatus) venom. Toxicon. 1981;19(6):889–892. doi: 10.1016/0041-0101(81)90086-6. [DOI] [PubMed] [Google Scholar]
  16. Hokama Y., Iwanaga S., Tatsuki T., Suzuki T. Snake venom proteinase inhibitors. III. Isolation of five polypeptide inhibitors from the venoms of Hemachatus haemachatus (Ringhal's corbra) and Naja nivea (Cape cobra) and the complete amino acid sequences of two of them. J Biochem. 1976 Mar;79(3):559–578. doi: 10.1093/oxfordjournals.jbchem.a131100. [DOI] [PubMed] [Google Scholar]
  17. Howard B. D., Gundersen C. B., Jr Effects and mechanisms of polypeptide neurotoxins that act presynaptically. Annu Rev Pharmacol Toxicol. 1980;20:307–336. doi: 10.1146/annurev.pa.20.040180.001515. [DOI] [PubMed] [Google Scholar]
  18. Joubert F. J., Strydom D. J. Snake venoms. The amino-acid sequence of trypsin inhibitor E of Dendroaspis polylepis polylepis (Black Mamba) venom. Eur J Biochem. 1978 Jun 1;87(1):191–198. doi: 10.1111/j.1432-1033.1978.tb12366.x. [DOI] [PubMed] [Google Scholar]
  19. Joubert F. J., Taljaard N. Snake venoms. The amino acid sequences of two proteinase inhibitor homologues from Dendroaspis angusticeps venom. Hoppe Seylers Z Physiol Chem. 1980 May;361(5):661–674. doi: 10.1515/bchm2.1980.361.1.661. [DOI] [PubMed] [Google Scholar]
  20. Kelly R. B., Deutsch J. W., Carlson S. S., Wagner J. A. Biochemistry of neurotransmitter release. Annu Rev Neurosci. 1979;2:399–446. doi: 10.1146/annurev.ne.02.030179.002151. [DOI] [PubMed] [Google Scholar]
  21. Kondo K., Narita K., Lee C. Y. Amino acid sequences of the two polypeptide chains in beta1-bungarotoxin from the venom of Bungarus multicinctus. J Biochem. 1978 Jan;83(1):101–115. doi: 10.1093/oxfordjournals.jbchem.a131881. [DOI] [PubMed] [Google Scholar]
  22. Kondo K., Narita K., Lee C. Y. Chemical properties and amino acid composition of beta1-bungarotoxin from the venom of Bungarus multicinctus (Formosan banded krait). J Biochem. 1978 Jan;83(1):91–99. doi: 10.1093/oxfordjournals.jbchem.a131917. [DOI] [PubMed] [Google Scholar]
  23. Shipolini R. A., Bailey G. S., Edwardson J. A., Banks B. E. Separation and characterization of polypeptides from the venom of Dendroaspis viridis. Eur J Biochem. 1973 Dec 17;40(2):337–344. doi: 10.1111/j.1432-1033.1973.tb03202.x. [DOI] [PubMed] [Google Scholar]
  24. Strydom D. J. Protease inhibitors as snake venom toxins. Nat New Biol. 1973 May 16;243(124):88–89. [PubMed] [Google Scholar]
  25. Strydom D. J. Snake venom toxins. Purification and properties of low-molecular-weight polypeptides of Dendroaspis polylepis polylepis (black mamba) venom. Eur J Biochem. 1976 Oct 1;69(1):169–176. doi: 10.1111/j.1432-1033.1976.tb10870.x. [DOI] [PubMed] [Google Scholar]

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